Recent advances in developing polymeric micelles for treating cancer: Breakthroughs and bottlenecks in their clinical translation

Drug Discovery Today, Journal Year: 2022, Volume and Issue: 27(5), P. 1495 - 1512

Published: Feb. 11, 2022

Language: Английский

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Functionalized nanoparticles: Tailoring properties through surface energetics and coordination chemistry for advanced biomedical applications

Nanoscale, Journal Year: 2023, Volume and Issue: 15(13), P. 6075 - 6104

Published: Jan. 1, 2023

Significant advances in nanoparticle-related research have been made the past decade, and amelioration of properties is considered utmost importance for improving nanoparticle bioavailability, specificity, catalytic performance. Nanoparticle can be tuned through in-synthesis post-synthesis functionalization operations, with thermodynamic kinetic parameters playing a crucial role. In spite robust techniques based on surface chemistry, scalable technologies not explored well. The coordination enhancement via organic/inorganic/biomolecules material has attracted much attention morphology modification shape tuning, which are indispensable aspects colloidal phase during biomedical applications. It envisioned that influences anchoring nano interfaces immobilization functional groups biomolecules. this work, various nanostructure methodologies discussed, aiming to exploit their full potential precision engineering Simultaneous discussions emerging characterization strategies functionalized assemblies gain insights into chemistry. An overview current prospects nanoparticles presented, an emphasis controllable attributes such as size, shape, morphology, functionality, features, Debye Casimir interactions.

Language: Английский

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HGTDR: Advancing drug repurposing with heterogeneous graph transformers

Bioinformatics, Journal Year: 2024, Volume and Issue: 40(7)

Published: June 24, 2024

Abstract Motivation Drug repurposing is a viable solution for reducing the time and cost associated with drug development. However, thus far, proposed approaches still need to meet expectations. Therefore, it crucial offer systematic approach achieve savings enhance human lives. In recent years, using biological network-based methods has generated promising results. Nevertheless, these have limitations. Primarily, scope of generally limited concerning size variety data they can effectively handle. Another issue arises from treatment heterogeneous data, which needs be addressed or converted into homogeneous leading loss information. A significant drawback that most lack end-to-end functionality, necessitating manual implementation expert knowledge in certain stages. Results We propose new solution, Heterogeneous Graph Transformer Repurposing (HGTDR), address challenges repurposing. HGTDR three-step graph-based repurposing: (1) constructing graph, (2) utilizing graph transformer network, (3) computing relationship scores fully connected network. By leveraging HGTDR, users gain ability manipulate input graphs, extract information diverse entities, obtain their desired output. evaluation step, we demonstrate performs comparably previous methods. Furthermore, review medical studies validate our method’s top 10 suggestions, exhibited also demonstrated HGTDR’s capability predict other types relations through numerical experimental validation, such as drug–protein disease–protein inter-relations. Availability The source code are available at https://github.com/bcb-sut/HGTDR http://git.dml.ir/BCB/HGTDR

Language: Английский

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Leveraging disulfiram to treat cancer: Mechanisms of action, delivery strategies, and treatment regimens

Biomaterials, Journal Year: 2021, Volume and Issue: 281, P. 121335 - 121335

Published: Dec. 28, 2021

Language: Английский

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Structural characterization and antitumor activity of a polysaccharide from Dendrobium wardianum

Carbohydrate Polymers, Journal Year: 2021, Volume and Issue: 269, P. 118253 - 118253

Published: May 28, 2021

Language: Английский

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In vitro anticancer activity of Eclipta alba whole plant extract on colon cancer cell HCT-116

BMC Complementary Medicine and Therapies, Journal Year: 2020, Volume and Issue: 20(1)

Published: Nov. 23, 2020

Abstract Backgrounds Colon cancer is the third most deadly and one of diagnosed diseases in world. Although routine screening early detection during last decades has improved survival, colon still claims hundreds thousands lives each year worldwide. Surgery chemotherapy mainstay current treatment, nevertheless toxicity associated with this treatment underscores urgency demand a better therapeutics. Close to 50% chemotherapeutic drugs are direct or indirect descendants compounds isolated from medicinal plants, which indicate plants great potential sources novel In our literature review we found Eclipta alba posses many pharmacological activities, including those anticancer potentials. However, no study on activity kind been reported. Methods Phytochemicals were extracted by maceration method shade dried whole plant using methanol as solvent. The effect extract was investigated various cell lines like human colorectal carcinoma (HCT-116), prostate (PC-3), Michigan foundation-breast (MCF-7) renal (RCC-45). We have also studied effects normal embryonic lung fibroblast (WI-38) MTT (methyl thiazoldiphenyltetrazolium bromide) assay, clonogenic (colony formation) migration assay. Finally obtained results analyzed ANNOVA Dunnett’s test. Results assay revealed that methanolic carried significant ( p < 0.005) specificity against HCT-116 cells compared other cells. This showed minimal nontoxicity WI-38 Migration well assays confirmed Conclusion unique finding its because specific not reported extract. opens up possibility develop antitumor drug candidate future.

Language: Английский

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Drugs repurposed: An advanced step towards the treatment of breast cancer and associated challenges

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 145, P. 112375 - 112375

Published: Dec. 1, 2021

Breast cancer (BC) is mostly observed in women and responsible for huge mortality subjects globally. Due to the continued development of drug resistance other contributing factors, scientific community needs look new alternatives, repurposing one best opportunities. Here we light upon with a major focus on breast cancer. BC division known as leading cause death 2.3 million globally, 685,000 fatalities. This number steadily rising, necessitating treatment that can extend survival time. All available treatments are very costly well show side effects. unfulfilled requirement anti-cancer drugs ignited an enthusiasm repositioning, which means finding out use already marketed complications. With advancement proteomics, genomics, computational approaches, process hastens. So many repurposed BC, including alkylating agents, antimetabolite, anthracyclines, aromatase inhibitor, mTOR, more. The so reviewing how challenges be combated repurposing. paper provides updated information all candidates molecular mechanism their anti-tumor activity. Additionally, occur during discussed.

Language: Английский

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Druggable genome and precision medicine in cancer: current challenges

FEBS Journal, Journal Year: 2021, Volume and Issue: 288(21), P. 6142 - 6158

Published: Feb. 24, 2021

The past decades have seen tremendous developments with respect to "specific" therapeutics that target key signaling molecules conquer cancer. advancements multiomics technologies, especially genomics, allowed physicians and molecular oncologists design "tailor-made" solutions the specific oncogenes are deregulated in individual patients, a strategy which has turned out be successful though patients quickly develop resistance. swift integration of multidisciplinary approaches led development "next generation" and, synergistic therapeutic regimes combined immune checkpoint inhibitors reactivate dampened response, provided much-needed promise for cancer patients. Despite these advances, large portion druggable genome remains understudied, role system needs further attention. Establishment patient-derived organoid models fastened preclinical validation novel clinical translation. We summarized current advances challenges also stress importance biobanking collection longitudinal data sets structured information, as well critical "high content sets" will play designing new tailor-made fashion.

Language: Английский

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Inhibition of NPC1L1 disrupts adaptive responses of drug‐tolerant persister cells to chemotherapy

EMBO Molecular Medicine, Journal Year: 2022, Volume and Issue: 14(2)

Published: Jan. 13, 2022

Article13 January 2022Open Access Source DataTransparent process Inhibition of NPC1L1 disrupts adaptive responses drug-tolerant persister cells to chemotherapy Zhe Zhang orcid.org/0000-0001-7509-6965 Laboratory Aging Research and Cancer Drug Target, State Key Biotherapy Center, National Clinical Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, School Basic Medical Sciences & Forensic Medicine, Collaborative Innovation Biotherapy, Contribution: Conceptualization, Data curation, Visualization, Writing - original draft, review editing Search more papers by this author Siyuan Qin Methodology Yan Chen Li Zhou curation Mei Yang orcid.org/0000-0002-0423-6358 Yongquan Tang Department Pediatric Surgery, Jing Zuo Jian Southern University Science Technology Shenzhen, Guangdong, Guangdong Provincial Cell Microenvironment Disease Research, Atsushi Mizokami Urology, Graduate Sciences, Kanazawa Kanazawa, Japan Edouard C Nice Biochemistry Molecular Biology, Monash Clayton, Vic, Australia Supervision, Hai-Ning Corresponding Author [email protected] orcid.org/0000-0003-0104-8498 Gastrointestinal Funding acquisition, Methodology, Canhua Huang orcid.org/0000-0003-2247-7750 Validation, Project administration Xiawei Wei orcid.org/0000-0002-6513-6422 administration, Information Zhang1,2,†, Qin2,†, Chen2,†, Zhou2, Yang2, Tang3, Zuo2, Zhang4,5, Mizokami6, Nice7, *,8, *,2 *,1 1Laboratory 2State 3Department 4School 5Guangdong 6Department 7Department 8Department † These authors contributed equally work *Corresponding author. Tel: +86 18980606468; E-mail: 13258370346; 18081954096; EMBO Mol Med (2022)14:e14903https://doi.org/10.15252/emmm.202114903 PDFDownload PDF article text main figures. Peer ReviewDownload a summary the editorial decision including letters, reviewer comments feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures Info Abstract Entering (DTP) state cancer is transient self-adaptive mechanism which residual cell subpopulation accelerates tumor progression. Here, we identified acquisition DTP phenotype in multidrug-resistant (MDR) as tolerance response routine combination treatment. Characterization MDR with RNA-seq revealed that these partially prevented chemotherapy-triggered oxidative stress promoting NPC1L1-regulated uptake vitamin E. Treatment inhibitor ezetimibe further enhanced therapeutic effect combinatorial therapy inducing methuosis. Mechanistically, demonstrated NRF2 was involved transcriptional regulation binding −205 −215 bp site on its promoter. Decreased DNA methylation also related process. Furthermore, confirmed triple-combination chemotherapeutic agents, verapamil, ezetimibe, had significant anti-tumor recurrence mice. Together, our study provides novel insight into role emphasizes importance disrupting redox homeostasis during therapy. Synopsis Drug-tolerant driver failure relapse. This key state, where orchestrated signaling against harsh environment caused possess stronger capacity enter than non-resistant cells. supporter counter therapy-induced inhibition interrupts E cholesterol, triggering lipid ROS accumulation consequent lipotoxicity agents/verapamil treatment A exerts prevents The paper explained Problem mostly due occurrence multidrug resistance (MDR). subset exhibits entering after emerging concept explains generation resistant clones clinically relevant MDR. Accordingly, exploring specific behavior current important delaying or even eradicating targeting vulnerabilities. Results We MDR1-mediated agents MDR1 verapamil. survived chemotherapy-induced primarily scavenging through NRF2-NPC1L1 axis-regulated uptake. Based nanoparticle-related drug delivery systems alleviate verapamil side effects vivo, Impact Our bearings relationship between NPC1L1-modulated defense using cells, establishes strategy treating preventing recurrence. Introduction resistance, either intrinsic acquired, omnipresent clinical cancer, limiting durable benefits accelerating metastasis (Szakacs et al, 2006; Andrei 2020; Dallavalle 2020). Multidrug one most difficult problems occurring chemotherapy, commonly expression ATP-binding cassette (ABC) transporters, especially transporter—multidrug protein 1 (MDR1) encoded ABCB1 (Hall 2009). Along emergence appropriate analytical tools, advanced medicinal techniques, multidisciplinary research, ample evidence not only identifies high portending poor adverse outcomes patients cancers but confirms necessity applying new protocols prevent clinic (Fan 2017). Unfortunately, growing realization rather being sensitive resistant, can be dynamic nature within context detracting from such studies (Qin There actually, particular lying sensitivity termed "drug-tolerant state," population endowed dormant, slow-cycling stem-like signature (Shen 2019, originates an early observation bacterial antibiotics, existence bacteria exposed antibiotics non-genetic variations resumption their initial characteristics upon interruption (Balaban 2019). In share similar situation is, fashion antibiotic driven epigenetic inheritance variant gene patterns. could result inhibiting efficacy providing reservoir evolution Given has been hypothesized part alternative approach toward bona fide mechanism, line research attracting considerable attention. addition recognition serve target (i.e., incorporation modulator), focusing have deepened understanding mechanisms driving DTP. encourages development methods aimed at disposing sustaining harmless dormant reactivating proliferation enhance anti-proliferative drugs eradicate them (Recasens Munoz, However, there remains some confusion how best indicating requirement both itself DTP-mediated order devise countermeasures persisters. To date, multiple emphasized impact generation, several teams highlighted adapt common characteristic (Raha 2014; Sahu 2016; Hangauer 2017; Anand 2019; Dhimolea 2021). characteristic, increasing numbers targets investigated. Among phospholipid glutathione peroxidase 4 (GPX4) crucial survival therapy-resistant state. context, subsequent shown GPX4-dependent almost completely induction ferroptosis, death, suggesting potential disturbing (Hangauer Additionally, activated NF-E2-related factor 2 (NRF2), detected HER2-inhibited persistent breast found drive re-establishment metabolism-dependent manner, thereby reactivation triggered glutaminase inhibition. impair growth recurrent tumors levels NRF2, treat (Fox Such findings confirm adaption stress. might raise robust antioxidant system resisting (Trachootham therefore questioned whether arising prefer orchestrate evolutionarily conserved study, investigated characterized overexpression underwent (chemotherapeutic agent verapamil)-induced gain alterations profile course non-mutationally acquired performed comparing function screened genes status. NPC1L1, regulator interact directly peroxyl radicals, thus stress, highly expressed By adding therapy, absorption compromised additional death observed consequence macropinocytosis induction. results link activation decreased expression. Using nanomedicine triple-combinatorial (a ezetimibe) vivo. progresses persistence perspective, repositioning Oncotherapy induces transformation elucidate molecular underlying established drug-resistant models (Du145TXR taxol; MCF-7ADR adriamycin) (Appendix Fig S1A B), first examined (also known p-glycoprotein), extensively studied (Gouaze 2005; Takeda 2007; Robey 2018) marked upregulation S1C). determined played regulating rhodamine123 substrate MDR1) Fluorescence analysis indicated expressing showed increased efflux compared control reverse S1D). investigate anti-cancer ability synergistic effects, viability Chou–Talalay method (combination index (CI) < representing synergism) different combination-treated 50 μM combined 20 nM taxol 200 adriamycin exhibited beneficial Du145TXR S1E F). significantly inhibited under treatment, evidenced reduced colony formation S2A B). Consistently, knockdown clearly clonogenic chemotherapy-treated S2C–G). Together previous reports, data support establish MDR1, least part, enables recover chemosensitivity. Notably, following were those described survive cytotoxic exposure via reversible non-mutational mechanisms. evaluate associated morphological changes (50 verapamil/20 adriamycin). Surprisingly, (MCs), treated (RMCs) dramatic 3 days obvious second applied 1, 3, 6, 9 withdrawal assay (Fig 1A–D). Subsequently, long-term "drug holiday" (30 days) allowed regrow (regrown RCs) resulted re-acquisition 1E). reversibility implies oncotherapy drives (MPCs). compare differences MPCs (PeCs), used protocol generate (CCs) EV1A). prolonged > small EV1B–D). addition, progressively re-acquired eventually became non-differential Day 6 EV1E converted above obtained assays (Figs 1C–E EV1C–F) rate. As 1F G, evolve faster longer duration Taken together, demonstrate transform resembling possibly leading worse outcome modest reversal Figure 1. A. Schematic analyses. circular arrow represents B. Phase contrast images regrown MCF-7ADR. Red circles mark magnified areas (bottom). Scale bars, μm (low magnification images). C, D. (MCs) (C) (D) same 24 h days. Student's t-test analyze statistical differences. Mean ± SD. (RCs) (left) (right) h. F, G. rate (F) Du145/Du145TXR (20 taxol/20 plus verapamil) (G) MCF-7/MCF-7ADR (200 adriamycin/200 defined followed RMCs vs. MCs CCs PeCs, tolerant. Induction time indicates state; maintaining Blue colors represent groups; information: are representative three independent experiments. available online figure. [emmm202114903-sup-0004-SDataFig1.jpg] Download figure PowerPoint Click here expand EV1. Control states change Du145 MCF-7 72 bar, (low-magnification (CCs), (CCs-3), (PeCs) concentrations (TAX) (ADM) E, F. CCs, withdrawn PeCs (PeCs-3), (PeCs-6) (E) Upregulation supports well-known cycle arrest, stemness markers, well epithelial–mesenchymal transition (EMT) 2020), phenotypes. seemed increases p27 p21 S3A). flow cytometry arrest G0/G1 phase induced MPCs, showing non-proliferative slowly proliferative S3B–D). markers ALDH1A1, Oct-4A, Sox2, KLF4, CD44 sphere self-renewal stemness, increase number size spheres S3E–G). Interestingly, ALDH1A1 CM10 selectively lethal sensitized consistent Appendix S3H–J). characteristics, downregulat

Language: Английский

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Cubosomes in cancer drug delivery: A review

Colloids and Interface Science Communications, Journal Year: 2021, Volume and Issue: 46, P. 100561 - 100561

Published: Dec. 7, 2021

The lyotropic nonlamellar liquid crystalline nanoparticles (LCNs), especially cubosomes are gaining utility and acceptance as a drug delivery system, in diseases like cancer. These highly versatile carriers with promising theranostic efficiency can be administered via oral, topical, or intravenous modalities. Over the recent years, significant research has facilitated improvement efficacy, preparation, characterization, target selectivity, controlling release profiles of loaded anticancer bioactive. Nonetheless, its clinical translation been slow additionally requires concrete evidence. This review underscores advances impediments development application against various cancers discussing hurdles faced segueing it into potential nanotechnological intervention.

Language: Английский

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